Kallikreins and kallikrein-like proteins are a subgroup of the serine protease enzyme family and exhibit a high degree of substrate specificity (1). The biological role of these kallikreins is the selective cleavage of specific polypeptide precursors (substrates) to release peptides with potent biological activity (2). In mouse and rat, kallikreins are encoded by large multigene families. In the mouse genome, at least 24 genes have been identified (3). Expression of 11 of these genes has been confirmed; the rest are presumed to be pseudogenes (4). A similar family of 15–20 kallikreins has been found in the rat genome (5) where at least 4 of these are known to be expressed (6).
Three human kallikrein genes have been described, i.e. prostatic specific antigen (PSA or KLK3) (7), human glandular kallikrein (KLK2) (8) and tissue (pancreatic-renal) kallikrein (KLK1) (9). The PSA gene spans 5.8 Kb of sequence which has been published (7); the KLK2 gene has a size of 5.2 Kb and its complete structure has also been elucidated (8). The KLK1 gene is approximately 45 Kb long and the exon sequences and the exon/intron junctions of this gene have been determined (9).
The mouse kallikrein genes are clustered in groups of up to 11 genes on chromosome 7 and the distance between the genes in the various clusters can be as small as 3–7 Kb (3). All three human kallikrein genes have been assigned to chromosome 19q13.2–19q13.4 and the distance between PSA and KLK2 has been estimated to be 12 Kb (9).
A major difference between mouse and human kallikreins is that two of the human kallikreins (KLK2 and KLK3) are expressed almost exclusively in the prostate while in animals none of the kallikreins is localized in this organ. Other candidate new members of the human kallikrein gene family include protease M (10) (also named Zyme (11) or neurosin (12) and the normal epithelial cell-specific gene-1 (NES1) (13). Both genes have been assigned to chromosome 19q13.3 (10,14) and show structural homology with other serine proteases and the kallikrein gene family (1114).